This is a multidisciplinary collaboration between investigators at the Massachusetts Institute of Technology and the VA Boston Healthcare System integrating imaging technology research, clinical imaging studies, medical device development and animal imaging studies. Esophageal cancer is a lethal malignancy, with a five-year survival rate of 16%. Barrett's esophagus (BE) and dysplasia are precursors to esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) is becoming the standard of care as an effective treatment for dysplastic BE, greatly reducing progression to malignancy. However, RFA requires an average of >3 treatment sessions, and long term recurrence rates for BE are >25%. Optical coherence tomography (OCT) can perform high resolution, three-dimensional imaging of tissue morphology in situ and in real-time. The hypotheses are: 1. Endoscopic OCT can identify features associated with RFA treatment response, 2. Image guided ablation therapy can be developed for treatment planning and real time ablation monitoring, and 3. Image guidance can reduce sampling errors and increase yields for excisional biopsy diagnosis of dysplasia and early carcinoma. Aim 1: Endoscopic OCT markers for RFA treatment response. We will conduct a prospective, longitudinal study on patients with dysplastic BE being treated with RFA to identify structural features associated with RFA treatment response. Endoscopic OCT will be performed to volumetrically map markers including BE epithelium thickness, subsquamous intestinal metaplasia, and residual glandular structure due to insufficient ablation. We will evaluate the correlation of these features to RFA treatment efficacy/durability, including the total number of treatment sessions and recurrence of BE post treatment. Aim 2: Image guided esophageal ablation devices and techniques. OCT enables real time imaging of esophageal structure and ablation depth. We propose to develop and compare an OCT-guided multi-zone RFA ablation probe and OCT-guided laser ablation balloon. Studies will be performed on swine esophagus ex vivo to establish dosing parameters using OCT imaging and histological validation. An in vivo swine model will then be used to evaluate the ability to simpliy ablation protocols and to perform controlled depth and area ablations. Aim 3: Ultrahigh resolution endoscopic OCT for detecting dysplasia and early carcinoma. Detecting dysplasia and early carcinoma remains challenging and the standard diagnostic procedure relies on four quadrant biopsy sampling. We propose to develop ultrahigh speed swept source OCT and probe technologies for dysplasia and early carcinoma detection. Validation studies will be performed in patients with upper GI dysplasia and patients with lower GI endoscopic mucosal resection (EMR) to assess sensitivity and specificity of OCT imaging compared with standard histology. The proposed work will develop new imaging methods that could risk stratify RFA patients, enable future image guided clinical ablation devices, and increase sensitivity for dysplasia and early carcinoma diagnosis.